CRCNS: Cholinergic contribution to hippocampal information processing

CRCNS：胆碱能对海马信息处理的贡献

• 批准号: 10183326
• 负责人: Carmen Castro Canavier
• 金额: $ 36.5万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10183326
• 关键词: Acetylcholine; Affect; Area; Attenuated; Behavior; Buffers; Cations; Cells; Code; Cognition Disorders; Cognitive Therapy; Complex; Computer Models; Data; Diffuse; Dose; Electrophysiology (science); Environment; Fire - disasters; Frequencies; Hippocampus (Brain); Image; Individual; Ion Channel; Lead; Learning; Location; Mediating; Memory; Mental disorders; Modeling; Myoepithelial cell; Neuromodulator; Neurons; Parvalbumins; Pattern; Pharmacology; Phase; Physiologic pulse; Play; Positioning Attribute; Process; Property; Pyramidal Cells; Ramp; Rattus; Recording of previous events; Retrieval; Role; Route; Sensory; Shapes; Slice; Stream; Structure; Synapses; Synaptic plasticity; Testing; Therapeutic; Visit; Work; attenuation; base; cholinergic; entorhinal cortex; experimental study; hippocampal pyramidal neuron; improved; in vivo; information processing; model development; neurotransmitter release; optogenetics; patch clamp; place fields; predictive modeling; prospective; relating to nervous system; response; two-photon

Area CA 1 of the hippocampus plays a key role in learning and memory. CA 1 pyramidal neurons receive two major input streams, one from the entorhinal cortex that mediates sensory information about the external world, and another from area CA3 that mediates retrieval of previously stored representations. The neuromodulator acetylcholine (ACh) is thought to gate encoding and retrieval. Our preliminary results indicate that ACh, by activating the Ca2+-activated nonspecific cation current ICAN and modulating other ion channels, dramatically affects the intrinsic response to a triangular current ramp simulating the excitatory input, thus levels of ACh may regulate the pattern of place field firing by shifting the peak to later positions in ramp. This shift could cause the coding to shift from prospective, representing upcoming locations, to retrospective, representing recently visited locations, which may favor encoding over retrieval. Our preliminary data also shows that ACh can induce sustained firing; since novelty increases ACh levels, this persistent firing may facilitate the synaptic plasticity required to form new place fields. Moreover, we find that there are both intrinsic and synaptic mechanisms that endow CA 1 pyramidal neurons with low pass filtering capabilities specific to the Schaffer collateral (SC) inputs from CA3, and that these capabilities are switched off by ACh. In Aim 1, we test the hypothesis that cholinergic modulation converts the shape of the rate response to a triangular current ramp from decelerating to accelerating in a dose-dependent fashion, with a concomitant shift in the peak. In Aim 2, we test the hypotheses that intrinsic properties of CA 1 neurons mediate low pass filtering of SC inputs, with a critical additional component provided by parvalbumin-positive (PV+) basket cells, and that cholinergic modulation removes the low pass filtering, such that CA 1 can follow higher input frequencies from CA3. This work seeks to elucidate the neural bases of complex behaviors and mental illnesses. Better understanding of the mechanisms underlying cholinergic modulation of neuronal ensembles may lead not only to an improved understanding of information processing important in learning and memory, but eventually to improved therapies for cognitive disorders.

海马CA1区在学习和记忆中起着关键作用. CA 1锥体神经元接受两个 主要的输入流，一个来自内嗅皮层，介导关于外部的感觉信息 另一个来自区域CA3，其调解先前存储的表示的检索。的 神经调质乙酰胆碱（ACh）被认为是门控编码和检索。我们的初步结果 表明ACh通过激活Ca 2+激活非特异性阳离子电流ICAN和调节其它 离子通道，显着影响固有的反应，以三角形电流斜坡模拟兴奋性 因此，ACh的水平可以通过将峰值移动到输入的较后位置来调节位置场激发的模式。 斜坡。这种转变可能导致编码从表示即将到来的位置的预期转变为 回溯，表示最近访问过的位置，这可能有利于编码而不是检索。我们 初步数据还表明，ACh可以诱导持续放电;由于新奇感会增加ACh水平， 持续的激发可以促进形成新位置场所需的突触可塑性。此外，我们发现， CA1区锥体神经元具有低通滤波的内在机制和突触机制 特定于来自CA3的Schaffer附属品（SC）输入的能力，并且这些能力被切换 由ACh。在目标1中，我们检验了胆碱能调节改变了速率形状的假设。 以剂量依赖性方式对三角形电流斜坡从减速到加速的响应， 峰的伴随移动。在目标2中，我们测试了假设，CA 1神经元的内在属性 SC输入的介导低通滤波，由小白蛋白阳性提供关键的附加组件 (PV+）篮状细胞，胆碱能调节消除了低通滤波，这样CA 1就可以跟随 来自CA3的更高输入频率。这项工作旨在阐明复杂行为的神经基础， 精神疾病更好地理解神经元胆碱能调节的机制 合奏不仅可以提高对学习中重要的信息处理的理解， 和记忆，但最终改善了认知障碍的治疗方法。

项目成果

Phase response theory explains cluster formation in sparsely but strongly connected inhibitory neural networks and effects of jitter due to sparse connectivity.

相位响应理论解释了稀疏但强连接的抑制神经网络中的簇形成以及稀疏连接引起的抖动影响。

• DOI: 10.1152/jn.00728.2018
• 发表时间: 2019
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Tikidji-Hamburyan,RubenA;Leonik,ConradA;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC

Shunting Inhibition Improves Synchronization in Heterogeneous Inhibitory Interneuronal Networks with Type 1 Excitability Whereas Hyperpolarizing Inhibition Is Better for Type 2 Excitability.

分流抑制可改善具有 1 型兴奋性的异质抑制性中间神经元网络的同步性，而超极化抑制则更适合 2 型兴奋性。

• DOI: 10.1523/eneuro.0464-19.2020
• 发表时间: 2020
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Tikidji-Hamburyan,RubenA;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons.

钠通道的长期失活作为 CA1 锥体神经元的适应机制。

• DOI: 10.1523/jneurosci.1914-21.2022
• 发表时间: 2022
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Upchurch,CarolM;Combe,CrescentL;Knowlton,ChristopherJ;Rousseau,ValeryG;Gasparini,Sonia;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC